U.S. Pat. No. 4,258,041 describes the synthesis of (6R, 7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]- 3-(1-pyridiniummethyl)ceph-3-em-4-carboxylate, a cephalosporin antibiotic now generically known as ceftazidime. The reported synthesis of ceftazidime comprises reacting (Z)-2-(2-tert.-butoxycarbonylprop-2-oxyimino)-2-(2-triphenylmethylaminothi azol-4-yl)acetyl chloride with (6R,7R)-7-amino-3-(1-pyridiniummethyl)ceph-3-em-4-carboxylic acid in a mixture of N,N-dimethylacetamide and acetonitrile to provide the ceftazidime intermediate, (6R,7R)-7-[(Z)-2-(2-triphenylmethylaminothiazol-4-yl)-2-(2-tert.-butoxycar bonylprop-2-oxyimino)acetamido]-3-(1-pyridiniummethyl)ceph-3-em-4-carboxyla te. This ceftazidime intermediate was recovered from the reaction mixture as an amorphous solid that was subsequently purified by crystallization of an N,N-dimethylformamide solvate (21/2 moles of DMF per mole of intermediate) from N,N-dimethylformamide. The ceftazidime intermediate was then reacted with formic acid to effect removal of the protecting groups and to provide ceftazidime.
An object of the present invention is to provide an improved process for preparing the ceftazidime intermediate, whereby the intermediate is crystallized directly out of the reaction mixture as an N,N-dimethylacetamide solvate. The practice of this invention obviates the need for subsequent purification and thus provides improved yields and reduced costs in the production of ceftazidime.